PROJECT SUMMARY/ABSTRACT This career development award will provide Emily McGowan, MD with the skills, knowledge, and mentored research experience that are essential for an independent career as a clinician scientist in the field of allergy and immunology. Food allergy (FA) is a common childhood disease that appears to have increased in prevalence over the past two decades. The interplay between genes and the environment likely plays a key role in the development of FA, and DNA methylation is one possible mechanism by which environmental influences may affect gene expression. Several nutrients, including folate, vitamin B12, and choline, are involved in the one carbon metabolism pathway (OCMP), in which a methyl donor is transferred to DNA. In two separate cohorts, our group has shown an association between higher serum folate levels and the development of allergic sensitization, leading to our central hypothesis that differential exposure to folate, B12, and choline is associated with the development of food sensitization (FS) and FA, and that this is mediated by changes in DNAm. Dr. McGowan proposes to explore this hypothesis by examining 1) whether pre-natal or post-natal exposure to these OCMP micronutrients is independently associated with FS and FA; 2) whether differential exposure to these OCMP micronutrients is associated with DNA methylation; and 3) whether differentially methylated genes are associated with the development of FS and FA. In order to address these questions, Dr. McGowan will use two study populations: 1) a nested case-control study of children within the well-characterized Boston Birth Cohort (BBC) and 2) a new prospective cohort of 100 children at high risk for developing FA. Given the widespread exposure to methyl donors through formula and supplements in infancy, the results of this study could have major public health implications. In addition, this K23 award will provide Dr. McGowan with opportunities for advanced training in epidemiology, including the completion of a PhD in Clinical Investigation at the Johns Hopkins Bloomberg School of Public Health (JHBSPH). She will also pursue training to develop new skills in the analysis and interpretation of epigenomic data. Dr. McGowan plans to achieve these goals through formal coursework, workshops, national meetings, and mentored research. Her primary mentor for this award is Dr. Xiaobin Wang, a molecular epidemiologist who studies genetic and environmental predictors of childhood health. Her mentoring team further includes Drs. Robert Wood, Elizabeth Matsui, Corinne Keet, Daniele Fallin, and Kasper Hansen, experts in food allergy, epidemiology, epigenetics, and statistics. This training plan, and the data generated from this proposed project, will provide the foundation needed to successfully transition to the role of an independent clinician scientist studying the epidemiology and treatment of food allergy.